决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Acute lymphocytic leukaemia.
分子治疗和免疫治疗的突破提高了治疗效果,同时降低了毒性,挑战了传统的2·5-3年强化化疗观念。
急性淋巴细胞白血病(ALL)是淋巴祖细胞的一种血液系统恶性肿瘤。增强的遗传学分析已识别出超过23种B细胞ALL亚型和17种T细胞ALL亚型。与此同时,高灵敏度可测量残留病灶检测方法的发展完善了疾病监测和风险分层。分子治疗和免疫治疗的突破提高了治疗疗效,同时降低了毒性,挑战了传统的2.5-3年强化化疗观念。显著进展包括使用更强效的BCR::ABL1酪氨酸激酶抑制剂,以及靶向CD19和CD22白血病表面抗原的抗体,这些在BCR::ABL1阳性ALL中带来了前所未有的结局。历史上,成人患者的结局比儿童病例更差,主要由于不良遗传亚型和较不利遗传亚型的患病率更高。然而,新疗法的开发已将B细胞ALL的总生存率提高至约80-90%,即使在成人和婴儿人群中也是如此。CAR-T 细胞疗法也改变了难治性或复发性ALL患儿的结局,目前正被纳入成人ALL的一线治疗。这些创新有望提高治愈率,同时减少对强化化疗和异基因干细胞移植的依赖。
Acute lymphocytic leukaemia (ALL) is a haematological malignancy of the lymphoid progenitor cells. Enhanced genetic analyses have led to the identification of over 23 subtypes of B-cell and 17 subtypes of T-cell ALL. In parallel, the development of highly sensitive measurable residual disease assays have refined disease monitoring and risk stratification. Breakthroughs in molecular therapeutics and immunotherapies have improved treatment efficacy while reducing toxicity, challenging the traditional notion of 2·5-3 years of intensive chemotherapy. Notable progress includes the use of more potent BCR::ABL1 tyrosine-kinase inhibitors, and antibodies targeting CD19 and CD22 leukaemia surface antigens, which have delivered unprecedented outcomes in BCR::ABL1-positive ALL. Historically, adults have had poorer outcomes than paediatric cases, largely due to the higher prevalence of adverse genetic subtypes and less favourable genetic subtypes. However, development of new therapies has improved overall survival in B-cell ALL to approximately 80-90%, even in adult and infant populations. Chimeric antigen receptor T-cell therapies have also transformed outcomes for children with refractory or relapsed ALL and are now being incorporated into the front-line treatment of adult ALL. These innovations hold the promise of increasing the cure rates while reducing reliance on intensive chemotherapy and allogeneic stem-cell transplantation.
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